The Gut Microbiome

Illustration by Megan Eloise/The Gazelle

A note to germaphobes: I recommend you stop reading now, because you are not going to like what is coming.

The Gut Microbiome

Scientists estimate that the total number of cells in the human body is somewhere around 37 trillion — human cells, that is. While 37 trillion is a number that is hard to conceptualize, it is nothing compared to the estimate of total bacterial cells living in and on us: bacteria outnumber human cells 10 to 1 — at least that’s everybody’s favorite trivia fact in microbiology. Regardless of what the number actually is, the point is that the bacteria with which we share our bodies are a force to be reckoned with; yet, until very recently, they have gone completely ignored.

Microbiome is the term we use to describe the populations of bacteria that naturally live on the surfaces of our bodies. The term as we understand it today may be less than two decades old, but we have learned incredible amounts about the microbes we harbor and what that relationship looks like. It turns out that these bacteria are not just using us as real estate; it seems the relationship is more equitable, and they perform a plethora of roles for us.

The microbiome is niche-specific — meaning the breakdown of the skin bacteria population is different from that of the vagina or the gut — and each play different roles. I am particularly interested in the bacteria that live in the gut.

One of my favorite papers, “The gut flora as a forgotten organ,” reviews some of the functions the gut microbiome fulfills:

1. They protect us against the disease-causing pathogenic bacteria by competing for space and resources, and more directly by secreting anti-microbial factors.

They strengthen the gut barrier that separates us from the outside world by inducing the gut to produce IgA, a type of immunoglobulin and cousin to the antibodies that circulate in the blood. IgA trains the immune system to recognize and only fight against pathogenic bacteria.
They help us process food. They help us break down foodstuff that we lack the enzymes to digest, produce vitamins, and facilitate the absorption of minerals.

I could go on for days lauding the microbiome, its infinite complexity and its immeasurable value to human health, but that might not be as interesting for you, the reader, as it would be for me. The takeaway point here is that we co-evolved with the microbiome and so these microbes are particularly adapted to play a role in our health that we do not yet completely understand.

Antibiotics & Obesity

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So what if we don’t understand the microbiome? As long as it’s there and it does its job, we can go on with our lives and ignore the little bugs that colonized you without your consent. The problem is that sometimes these bacteria aren’t there and so they can’t do their jobs.

Since at least the ‘60s, the agriculture industry has been mass-feeding antibiotics to livestock. Partly to curb the rampant infections that result from the poor conditions the animals are housed in, but also because, surprisingly, animals put on weight much faster on antibiotics. This happy phenomenon went unexplained for many years, but now we understand that it has to do with the effects of the antibiotics on the gut microbiota, the bacterial residents of the gut.

For my capstone, I worked with Dr Martin Blaser, whose lab focuses on trying to understand what antibiotics do to our microbial friends and what kind of repercussions that has on human health.

Specifically, we studied the effect of low-dose antibiotics and a high-fat diet on the physiology of mice and the composition of their microbiomes. To try to elucidate these changes, we split mice into four groups: (a) antibiotics and low fat diet, (b) antibiotics and high fat diet, (c) no antibiotics and low fat diet and (d) no antibiotics and high fat diet.

To study the changes in physiology, we looked at their weight change, their percentage fat mass, their hormone levels, etc. over time. To look at the microbiome, we took periodic stool samples, then extracted DNA from the stool for sequencing. By using a sequencing primer that targets a bacterial gene, we were able to separate bacteria DNA from from the mouse DNA coming from cells naturally shed from the intestine.

This gene, the 16S ribosomal RNA gene, was chosen because it is present in all bacteria with small variations that are species-specific. By looking up the genes we sequenced in gene databases and calculating their relative frequencies, we basically created a census of each mouse’s gut bacteria across the different time points that we could compare.

Putting this all together allowed us to make some interesting conclusions:

Low-dose antibiotics increased weight gain and body-fat percentage in mice, regardless of the type of diet the mice were on.

Antibiotics and high-fat diets are synergistic in weight promotion.

Both low-dose antibiotics and high-fat diet alter the structure of microbial communities in significant ways, and these disruptions persist over time.

What Does This Mean?

These results show that exposure to antibiotics and high-fat diets change the types of bacteria that live inside of us and their proportions. This has repercussions for our metabolism and may help explain today’s obesity and diabetes epidemic.

As always in science, there are still a lot of unanswered questions. How do these bacteria change our metabolism and physiology? Research shows that there are changes in the expressions of certain genes in at least the liver in response to altered microbes. Is this one of the ways changes in microbial compositions affect our bodies? How are bacteria in the intestine able to affect a different organ? Are these changes reversible? Can we use bacteria therapeutically?

Further research may help us figure out specifically which bacteria promote weight gain and which are protective against obesity and how. Such information could one day help us identify people at risk for obesity and obesity-related co-morbidities early enough for medical intervention, or may even help us devise therapies to curb obesity and even malnutrition. Serendipitously, a lot of the research on the role of the microbiome in malnutrition is happening here at Washington University School of Medicine, where I am now.

What I find particularly fascinating is that this is just the tip of the iceberg. More and more people are devoting time and resources into studying the microbiome and the disorders that arise when things go awry. Dysregulation of the microbiome has been associated with a wide range of conditions: Crohn’s disease, eczema, asthma and even depression. Everywhere we look there seems to be some microbial involvement. The microbiome could help us understand how these diseases develop, and eventually, how to better identify them, treat them more appropriately and prevent them all together.

The research in this article is a part of a larger investigation published by Cell on August 14 2014.

The Gut Microbiome